Trial results for a Phase 2 pilot study (NCT05144529) investigating evolocumab plus nivolumab/ipilimumab in treatment-naïve patients with metastatic NSCLC were posted on ClinicalTrials.gov on 2026-05-05. The combination arm showed a median progression-free survival (PFS) of 4.9 months and median overall survival (OS) of 12.7 months, compared to 12 months PFS and 27.3 months OS in the control arm.
Background
The study investigated the safety and tolerability of combining evolocumab with standard immunotherapy (nivolumab and ipilimumab) in people with advanced non-small cell lung cancer (NSCLC). Nivolumab (Opdivo™) and ipilimumab (Yervoy™) are immunotherapy drugs approved for advanced lung cancer with PD-L1 expression greater than or equal to 1%.
Trial design
The randomized pilot study (NCT05144529) was a Phase 2 trial that enrolled 19 participants with metastatic lung cancer. The study aimed to assess the safety and tolerability of combining evolocumab with nivolumab and ipilimumab. Participants were randomized to either the Ipilimumab/Nivolumab arm or the Ipilimumab/Nivolumab/Evolucumab arm. The trial was terminated.
Key results
The trial reported the following key measurements:
- For "Number of Participants With DLT (Dose-limiting Toxicity)": 0 Participants in the Ipilimumab/Nivolumab group and 0 Participants in the Ipilimumab/Nivolumab/Evolucumab group.
- For "Progression-free Survival (PFS)": The median PFS was 12 months for the Ipilimumab/Nivolumab group and 4.9 months for the Ipilimumab/Nivolumab/Evolucumab group.
- For "Overall Survival (OS)": The median OS was 27.3 months for the Ipilimumab/Nivolumab group and 12.7 months for the Ipilimumab/Nivolumab/Evolucumab group.
Other key measurements included:
- "Change in CD3+ Tumor Infiltrating Lymphocytes": In the Ipilimumab/Nivolumab group, the mean change was 7.132% (Standard Deviation: 6.053) and 15.246% (Standard Deviation: 27.088). In the Ipilimumab/Nivolumab/Evolucumab group, the mean change was 5.529% (Standard Deviation: 2.81) and 19.1% (Standard Deviation: 14.556).
- "Change in MHC-1 Expression": In the Ipilimumab/Nivolumab group, the mean change was 1.06 fold change (Standard Deviation: 0.24). In the Ipilimumab/Nivolumab/Evolucumab group, the mean change was 1.01 fold change (Standard Deviation: 0.22).
Key analyses included:
- A Cox Regression for "Cox Proportional Hazard" showed a value of 2.15 (95.0% CI: 0.71 to 6.55) with a p-value of 0.17.
- Another Cox Regression for "Cox Proportional Hazard" showed a value of 1.39 (95.0% CI: 0.42 to 4.65) with a p-value of 0.59.
- A Wilcoxon (Mann-Whitney) analysis for "Mean Difference (Net)" showed a value of 0.05 with a p-value of 0.41.
- A Fisher Exact analysis showed a p-value of 0.65.
What this means
This Phase 2 pilot study explored whether adding evolocumab could enhance the anti-tumor capabilities of nivolumab/ipilimumab immunotherapy in treatment-naïve patients with metastatic NSCLC. However, the results indicated the opposite, with the evolocumab combination arm showing notably shorter median progression-free survival (4.9 months vs 12 months) and overall survival (12.7 months vs 27.3 months) compared to the immunotherapy-alone arm. The trial was terminated, suggesting that this specific combination may not be beneficial and potentially detrimental for this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05144529, titled "A Randomized Pilot Study of Evolocumab Plus Nivolumab/Ipilimumab in Treatment-Naïve Patients With Metastatic NSCLC," were posted on 2026-05-05 on clinicaltrials.gov.